A Study on Intestinal Flora and Gut-liver Axis in Premature Infants with Parenteral Nutrition Associated Cholestasis Based on 16S rDNA Sequence Analysis
Objective The aim of this study was to investigate the intestinal microecological characteristics of premature infants with parenteral nutrition-associated cholestasis(PNAC)and the role of the gut-liver axis in the pathogenesis of PNAC.Methods This prospective study collected preterm infants admitted to the Neonatal Intensive Care Unit(NICU)of Zhongshan City People's Hospital from May 1,2020 to December 31,2022. During hospitalization period,patients received parenteral nutrition for more than 14 days.13 premature infants with PNAC were enrolled as the experimental group,while 24 neonates without PNAC as the control group.16S rDNA sequence analysis was used to determine the DNA status of fecal intestinal flora of the two groups.The level of inflammatory cytokines,including procalcitonin(PCT),Interleukin 6(IL-6)levels and liver and hepatobiliary biochemistry in the serum at different age groups were detected.The differences between the two groups were statistically analyzed.Results The results of this study showed that there were no significant differences between the experimental group and the control groups in the proportion of intestinal flora on the 1st,7thand14th days after birth(x2D1=0,x2D7=1.06,x2D14=6.98,P>0.05).There was a significant difference in the composition of the intestinal flora at the 30th day after birth(x2D30=16.29,P<0.05).The relative abundances of Firmicutes,Bacteroidetes and Proteobacteria were not significantly different between the two groups on the 7th day after birth(t value:0.69,2.00,2.00,P>0.05).The relative abundances of Firmicutes,Bacteroidetes and Proteobacteria were significantly different between the two groups on the 14th day after birth(t value:15.41,24.74,6.64,P<0.05 ).The relative abundance of Firmicutes, Bacteroidetes, Proteobacteria and Actinomycetes were also significantly different between the two groups on the 30th day after birth(t value:37.88,25.88,34.63,33.36,P<0.05).The results showed that the relative abundance of Firmicutes in the experimental group was lower than that in the control group on the 14th and 30th day after birth, while the relative abundance of Bacteroidetes, Proteobacteria and Actinomycetes in the experimental group were higher than that in the control group. Levels of serum Alanine transaminase(ALT),total bilirubin(T-BIL),direct bilirubin(D-BIL),total bile acid(TBA)and γ-glutamyltranspeptidase(γ-GT)were measured,which showed that levels of ALT,T-BIL, D-BIL,TBA and γ-GT in the experimental group were higher than those in the control group on the 14th , 30th and 60th day after birth.Serum levels of PCT and IL-6 in the experimental group were higher than those in the control group on the 14th and 30th day after birth and there were significant differences between the two groups(PCT:tD14=16.39,tD30=25.29,IL-6:tD14=7.03,tD30=9.65,P<0.05).The duration of parenteral nutrition(PN)in the experimental group was longer than that in the control group(22.0± 3.2d vs 17.8±3.1d,t=3.841,P<0.001).Conclusion Infants with PNAC and parenteral nutrition for more than 14 days have a different gut microbiota composition after 14 days old than those without PNAC.The intestinal flora of neonates with PNAC is dominated by Bacteroidetes and Proteobacteria from parenteral nutrition to postnatal days 14 and 30,and is accompanied by increased indexes of blood inflammation and aggravated cholestasis.Long duration of PN,the change of intestinal flora and the increase of inflammatory markers could be related to the occurrence and development of PNAC,and the specific mechanism needs further studies.
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